F. Tremel

Metastatic phaeochromocytoma: risks of diagnostic needle puncture and treatment by arterial embolisation.

A 62-year-old man had an acute episode of hypertension 72 h after fine needle aspiration biopsy of an intra- hepatic nodule. The patient had been operated 3 years previously for a right adrenal phaeochromocytoma with no evidence of metastases at that time. Thus, a relapse of the tumour was postulated and confirmed by raised levels of urinary metanephrines. The extent of the metastases precluded surgical intervention and thus localised embolisation was proposed and permitted a clinical stabilisation over 8 months. This case indicates the necessity of long-term post-operative follow-up of phaeochromocytoma as well as the dangers of fine needle aspiration biopsy of metastases from this kind of tumour. Treatment of malignant phaeochromocytoma is difficult and embolisation was a useful therapeutic alternative in this case where the metastases were well defined.

Should One Use Echocardiography or Contrast Transcranial Doppler Ultrasound for the Detection of a Patent Foramen Ovale after an Ischemic Cerebrovascular Accident

Patent foramen ovale is frequently associated with embolic cerebrovascular accidents. The diagnosis of patent foramen ovale is easier since the advent of transesophageal echocardiography. However, this method is semi-invasive and is not readily available in all units. Contrast transcranial Doppler ultrasound enables the detection of the passage of a contrast material injected into a peripheral vein to the cerebral circulation across an orifice which is most often a patent foramen ovale. Contrast transcranial Doppler ultrasound may facilitate, with a high sensitivity and specificity, the diagnosis of a patent foramen ovale when a transesophageal echo is not possible. However, transesophageal echocardiography remains the preferred test especially in the young since other potentially embolic sources, such as a thrombus in the left atrium, may be demonstrable.

Left ventricular hypertrophy and arterial hypertrophy.

In the most recent WHO recommendations of 1996 it was reiterated that the classification of HT still remains based on the actual BP figures but also on the importance of target organ lesions. Thus the study of cardiac and vascular function and in particular the presence of hypertrophy or remodeling is of importance. A limited number of studies have examined the prevalence, the association and the correlation between modifications and remodeling in the heart and in the vasculature. It is important to distinguish compliance vessels such as the carotid from resistance vessels such as the radial. For compliance vessels the prevalence of cardiac and vascular hypertrophy are nearly identical being around 5% for normotensive subjects and around 12% for hypertensive subjects. This prevalence of thickening in the intima-media is more evident in subjects with left ventricular hypertrophy (LVH). The left ventricular geometric pattern is also an element to take into account. The presence of concentric remodeling of the left ventricle without LVH has already been associated with an increase in intima-media thickness (IMT). When there is an LVH this IMT is similar in severity to the LVH and in particular concentric. For resistance vessels such as the radial artery the number of studies is limited but a significant correlation between left ventricular mean wall thickness and common carotid artery distensibility and compliance has been found. There is also a significant correlation between the radial median lumen ratio and the relative wall thickness but this correlation disappears when age and systolic BP are taken into account. Thus for this type of vessel it is too early to conclude the elements contributing to structural changes. The determinant factors for these structural changes in the heart and the carotid arteries associated with hypertension are certainly multiple be they haemodynamic, hormonal or genetic. The observation establishing an association between anomalies at cardiac and vascular level may have undoubted diagnostic, prognostic and therapeutic implications which are all intimately related and which require refinement and confirmation.

Effects of amlodipine on baroreflex and sympathetic nervous system activity in mild-to-moderate hypertension*

To investigate the effect of amlodipine on baroreflex sensitivity and sympathetic system activity, 36 patients with essential hypertension were randomized to once-daily, double-blind treatment with amlodipine 5 mg or placebo 5 mg for 60 days. Measurements with a Finapres device allowed calculation of baroreflex sensitivity and blood pressure (BP) variability. Adrenergic activity was assessed via measurements of lymphocyte beta2-adrenoceptors and plasma catecholamine concentrations. Compared with placebo, amlodipine significantly decreased BP, but did not significantly alter baroreflex sensitivity. Spectral analysis of Finapres data showed that, compared with placebo, amlodipine decreased the variability of systolic blood pressure, diastolic blood pressure, and RR interval in the low frequency band. There were no simultaneous changes in adrenergic function, however, suggesting that these effects of amlodipine were not mediated via sympathetic nervous system activation.

Diagnostic and prognostic value of exercise testing.

Summary: Measuring blood pressure during exercise under a standard protocol could be a useful diagnostic method in high‐risk patients and in borderline hypertensive subjects. It may also serve as an adapted test for hypertensive subjects undergoing physical activity at work or at leisure time with a particular cardiovascular work load. It can be used as a method of assessment to confirm the efficacy of an antihypertensive drug, and for prognostic evaluation of cardiovascular risk in terms of morbidity and mortality. An exercise blood pressure profile does not provide information about blood pressure during activities of daily living. For this purpose, ambulatory blood pressure measurement appears to be more relevant. Résumé: La mesure de la pression artérielle à l’effort dans le cadre d’un protocole standardisé apparait être un examen complémentaire important lors de l’étude de certains sujets: sur le plan diagnostique chez les sujets à “haut risque” et les hypertendus limites; sur un plan d’aptitude et d’orientation, chez les sujets hypertendus dont les activités professionnelles ou extra‐professionnelles impliquent une contrainte cardiovasculaire importante; sur un plan thérapeutique pour affirmer l’efficacité d’un médicament; et sur un plan pronostique, pour anticiper les facteurs de risque en terme de morbidité et de mortalité. Encore faut‐il bien réaliser que ces tests d’effort ne permettent pas d’apprécier les contraintes de la vie quotidienne, leur type, leur intensité et leur durée. C’est dans ce cadre que des mesures en ambulatoire paraissent se justifier.

Use of Ambulatory Blood Pressure Monitoring in the Management of Antihypertensive Therapy

SummaryThe recent development of ambulatory blood pressure (ABP) monitoring techniques has improved recording of blood pressure in therapeutic trials and in the clinical setting. The application of ABP differs according to which of these 2 applications is being considered.In therapeutic trials, a placebo control is required. The large quantity of precise data acquired with ABP monitoring allows the study of a limited number of patients; it also allows individual study of patients with a ‘white coat’ response (i.e. elevated blood pressure in response to examination by the clinician). Analysis of data from ABP monitoring may include the following: comparison of mean blood pressure values over 24 hours, daytime or night-time, or over any other selected time period; 24-hour blood pressure profiles, or analysis hour-by-hour, giving true chronotherapy, and providing data regarding the wearing-off of a drug effect or loss of therapeutic control; analysis of blood pressure at particular times, such as on waking; or specific examination of nonresponders.In individual patients, ABP monitoring should be reserved for specific indications. It can be used before initiation of treatment to confirm the necessity for treatment, especially in the context of hypertension at rest or the ‘white coat’ effect. With established treatment, ABP monitoring can be used in patients with resistant hypertension, in severe hypertension to examine loss of blood pressure control over time or inversion of the day/night cycle, and in patients with a specific illness, e.g. diabetes, in order to obtain the lowest blood pressure readings possible.Examination of these factors assists clinicians to accurately decide upon the timing and frequency of antihypertensive therapy.

Second-generation calcium antagonists and ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring (ABPM) is a particularly useful method for evaluating the effects of antihypertensive drugs. ABPM allows the therapeutic effect of an agent to be assessed continually by a large number of measurements, and the greater number of readings contributes to the higher degree of reproducibility associated with ABPM compared to other methods for measuring blood pressure. ABPM also enable measurements to be taken in “real-life” situations and removes the problem of observer bias. The number of patients required for clinical studies can be significantly reduced by using ABPM. It is still essential, however, to identify “white coat” subjects, placebo responders, and patients who do not respond to the treatment. ABPM studies have demonstrated that the novel dihydropyridine calcium antagonist, lacidipine, significantly reduces both systolic and diastolic blood pressures over a 24-h period, both during the day and at night. Furthermore, although the trough-to-peak ratios of many calcium antagonists have been shown to fall below the recommended level of 50%, lacidipine has a ratio above 60%. Other ABPM studies have also shown that lacidipine can correct the ‘early morning increase’ in blood pressure without effecting the 24-h nyethemeral profile.

Cardiac and vascular remodelling: effect of antihypertensive agents.

The 1996 World Health Organization (WHO) recommendations for mild hypertension stressed the need to evaluate target-organ lesions as treatment criteria. The effects of both vascular and heart remodelling on hypertension must to be taken into account, as they adversely influence the prognosis of patients with hypertension. It was previously demonstrated that at least three classes of antihypertensive agents were able to decrease morbidity and mortality in patients with hypertension. Meta-analyses have shown that angiotensin-converting enzyme inhibitors seem to have a marked effect on regression of left ventricular hypertrophy (LVH). However, the relationship between drug-induced LVH regression and reduced morbidity and mortality remains to be confirmed. The effect of antihypertensive agents on vascular hypertrophy, as assessed by intima-media thickness, and their involvement in reducing morbid events, also have to be determined at the vascular level. As experimental data have highlighted the involvement of angiotensin II in animal models of LVH and vascular hypertrophy development, the role of angiotensin II AT1 receptor blockers should also be assessed in this indication.

31 Spectral analysis of blood pressure variability in hypertensive patients with left ventricular hypertrophy

Objective To study the association between spectral analysis measurements of blood pressure and heart rate at rest in untreated essential hypertension, and their relationship with the development of left ventricular hypertrophy (LVH). Design and methods: Forty-one untreated hypertensives (25 men and 16 women; age, 50±12 years; range, 23–73 years) were measured at rest [World Health Organization (WHO) criteria, diastolic blood pressure (DBF) >90mmHg], by digital continuous photopledrysmography (Finapres 2300, 6mn of measurement in the dorsal decubitus position and standing up). Measurement of LVH pevereux criteria, left ventricular mass index (LVM), g/m2] to analyse two groups, LVM1+ (LVM1 >107 if female and 120 if male, n=19; LVMI=137±25) and LVMI- (n=22; LVMI=92±17). The overall variability is standard deviation (SD); spectral analysis variability (SA) is the Fast Fourier Transform of 256 points over three frequencies: low (0.004–0.07 Hz), medium (0.07–0.13 Hz) and high (0.13–0.5 Hz). Results were compared using the Wilcoxon test or one-way analysis of variance (age and sex). Results: By WHO criteria, systolic blood pressure (SBP) was significantly lower in the LVMI- group (153±10 versus 165±18, P<0.01), whereas DBF was not significantly different (94±6 versus 96±10 mmHg). By continuous measurement (Finapres) at rest there was no significant difference in SBP or DBF. On standing up SBP was significantly lower in the LVMI- group (148±20 versus 162±22mmHg, P<0.01). The SD of DBF at rest was higher in the LVMI- group (3.34 versus 3.06, P<0.05), but not significantly different standing up. There was no significant difference in SBP at rest (6.7 versus 6.32 mmHg) or standing (9.13 versus 11.5 mmHg). The spectral analysis of the medium frequency was significantly elevated in the LVMI- group at rest for SBP (3.56 versus 3.01 mmHg, P<0.05), DBF (1.99 versus 1.19mmHg, P<0.05) and heart rate (1.79 versus 1.77 beats/min, P<0.05). Spectral analysis of the low and high frequencies for SBP, DBF and heart rate did not show significant differences. Conclusion: These results are different from those obtained by invasive ambulatory measures. The spontaneous variability in blood pressure and heart rate at rest is increased when there is no cardiac effect (LVMI-). Spectral analysis shows that the increase in variability is due to an increase in the Mayer waves, suggesting an elevated adrenergic tone in hypertensive patients without LVH.